A Randomized Trial of Deep-Brain Stimulation for Parkinson's Disease

Humboldt-Universität zu Berlin, Berlín, Berlin, Germany
New England Journal of Medicine (Impact Factor: 55.87). 08/2006; 355(9):896-908. DOI: 10.1056/NEJMoa060281
Source: PubMed


Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management.
In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III).
Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P=0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P=0.08).
In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone. ( number, NCT00196911 [].).

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    • "Deep brain stimulation surgery (DBS) is a highly efficacious treatment option for patients with severe movement disorders such as Parkinson's disease (PD), dystonia and essential tremor (ET). Improvement in motor symptoms as well as quality of life have been proven in several multicenter studies for PD (Deuschl et al., 2006; Krack et al., 2003; Schupbach, 2005); for dystonia (Kupsch et al., 2006; Mueller et al., 2008; Vidailhet et al., 2005; Volkmann et al., 2012); and for ET (Hariz et al., 2008; Schuurman et al., 2000). "
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    ABSTRACT: To determine placement of electrodes after deep brain stimulation (DBS) surgery, a novel toolbox that facilitates both reconstruction of the lead electrode trajectory and the contact placement is introduced. Using the toolbox, electrode placement can be reconstructed and visualized based on the electrode-induced artifacts on post- operative magnetic resonance (MR) or computed tomography (CT) images. Correct electrode placement is essential for efficacious treatment with DBS. Post-operative knowledge about the placement of DBS electrode contacts and trajectories is a promising tool for clinical evaluation of DBS effects and adverse effects. It may help clinicians in identifying the best stimulation contacts based on anatomical target areas and may even shorten test stimulation protocols in the future. Fifty patients that underwent DBS surgery were analyzed in this study. After normalizing the post-operative MR/CT volumes into standard Montreal Neurological Institute (MNI)-stereotactic space, electrode leads (n = 104) were detected by a novel algorithm that iteratively thresholds each axial slice and isolates the centroids of the electrode artifacts within the MR/CT-images (MR only n = 32, CT only n = 10, MR and CT n = 8). Two patients received four, the others received two quadripolar DBS leads bilaterally, summing up to a total of 120 lead localizations. In a second reconstruction step, electrode contacts along the lead trajectories were reconstructed by using templates of electrode tips that had been manually created beforehand. Reconstructions that were made by the algorithm were finally compared to manual surveys of contact localizations. The algorithm was able to robustly accomplish lead reconstructions in an automated manner in 98% of electrodes and contact reconstructions in 69% of electrodes. Using additional subsequent manual refinement of the recon- structed contact positions, 118 of 120 electrode lead and contact reconstructions could be localized using the toolbox. Taken together, the toolbox presented here allows for a precise and fast reconstruction of DBS contacts by proposing a semi-automated procedure. Reconstruction results can be directly exported to two- and three- dimensional views that show the relationship between DBS contacts and anatomical target regions. The toolbox is made available to the public in form of an open-source MATLAB repository.
    NeuroImage 12/2014; 107:127-135. DOI:10.1016/j.neuroimage.2014.12.002 · 6.36 Impact Factor
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    • "The subthalamic nucleus (STN) is a common anatomical target for deep brain stimulation (DBS) for the treatment of Parkinson’s disease [1], and is being assessed for treatment of other disorders [2]–[4]. Over the past decade studies on subthalamic deep brain stimulation have looked for anatomical targets that optimize clinical outcomes [5]–[11]. "
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    ABSTRACT: The subthalamic nucleus (STN) is a common anatomical target for deep brain stimulation (DBS) for the treatment of Parkinson's disease. However, the effects of stimulation may spread beyond the STN. Ongoing research aims to identify nearby anatomical structures where DBS-induced effects could be associated with therapeutic improvement or side effects. We previously found that DBS lead location determines the rate - abrupt vs. gradual - with which therapeutic effect washes out after stimulation is stopped. Those results suggested that electrical current spreads from the electrodes to two spatially distinct stimulation targets associated with different washout rates. In order to identify these targets we used computational models to predict the volumes of tissue activated during DBS in 14 Parkinson's patients from that study. We then coregistered each patient with a stereotaxic atlas and generated a probabilistic stimulation atlas to obtain a 3-dimensional representation of regions where stimulation was associated with abrupt vs. gradual washout. We found that the therapeutic effect which washed out gradually was associated with stimulation of the zona incerta and fields of Forel, whereas abruptly-disappearing therapeutic effect was associated with stimulation of STN itself. This supports the idea that multiple DBS targets exist and that current spread from one electrode may activate more than one of them in a given patient, producing a combination of effects which vary according to electrode location and stimulation settings.
    PLoS ONE 08/2014; 9(8):e99663. DOI:10.1371/journal.pone.0099663 · 3.23 Impact Factor
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    • "The therapy substantially improves motor symptoms and quality of life while reducing medication requirements [1e3]. Currently, DBS is only approved for advanced PD and thus limited to patients for whom medications are no longer adequate [4] [5]. In the advanced stages of the disease, however , a significant portion of patients experience conditions or comorbidities that may make them ineligible for DBS. "
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    ABSTRACT: Background Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson’s disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Methods Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥ 6 months but < 4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n=15) or DBS+ODT (n=15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. Results As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. The DBS+ODT group took less medication at all time points, and this reached maximum difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS+ODT group suffered serious adverse events; remaining adverse events were mild or transient. Conclusions This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD.
    Parkinsonism & Related Disorders 07/2014; 20(7). DOI:10.1016/j.parkreldis.2014.03.019 · 3.97 Impact Factor
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